Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth-inhibitory activity of 2'-deoxycoformycin (DCF) and 9-beta-D-arabinofuranosyladenine (Ara-A) used either singly or in combination was assessed in 30 human cultured cell lines (seven T-cell, nine B-cell, five non-T,non-B and nine myeloid cell lines) derived from leukemias and lymphomas. DCF had little activity even at 100 microM on any of the cell lines, while Ara-A had an obvious inhibitory effect on them, especially on non-T,non-B cell lines at 10 microM or less. Lymphoid cell lines were apparently more sensitive to the combined use of Ara-A and DCF than myeloid cell lines. DCF potentiated the antiproliferative activity of Ara-A not only in T-cell lines with high adenosine deaminase (ADA) activity, but also in some other cell lines with low ADA activity. DCF was stable in the culture medium, but Ara-A in the medium containing cultured cells was rapidly inactivated. DCF completely inhibited the inactivation of Ara-A in the medium containing P12/ICH or NALM-6, but not in the medium containing Daudi. This suggests that there is some unknown mechanism(s) of inactivation of Ara-A other than ADA in Daudi, which was insensitive to Ara-A in the presence of 1 microM DCF. The capacity of DCF to inhibit degradation of Ara-A in the medium containing these cultured cells correlated with the level of Ara-A sensitivity potentiated by DCF. In all seven T-cell lines, seven of the nine B-cell lines, all five non-T,non-B cell lines, and only three of nine myeloid cell lines, the IC50 value for Ara-A decreased to 5 microM or less in the presence of 1 microM DCF. These results suggest that the combination of DCF and Ara-A may be effective against various types of lymphoid malignancies and some myeloid leukemias.
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PMID:Potentiation of growth-inhibitory activity of 9-beta-D-arabinofuranosyladenine by 2'-deoxycoformycin in human cultured cell lines derived from leukemias and lymphomas. 250 23

Asthma is a disease characterized by chronic relapsing airways, and its etiology remains incompletely understood. To better understand the metabolic phenotypes of asthma, we investigated a plasma metabolic signature associated with allergic asthma in ovalbumin (OVA)-sensitized mice by using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Sixteen metabolites were characterized as potential pathological biomarkers related to asthma. Among them, 6 (dodecanoic acid (P1), myristic acid (P2), phytosphingosine (P3), sphinganine (P4), inosine (P13) and taurocholic acid (P15)) were first reported to have potential relevance in the pathogenesis of experimental asthma. The identified potential biomarkers were involved in 6 metabolic pathways and achieved the most entire metabolome contributing to the formation of allergic asthma. Purine metabolism was the most prominently influenced in OVA-induced asthma mice according to the metabolic pathway analysis (MetPA), suggesting that significantly changes in inflammatory responses in the pathophysiologic process of asthma. The metabolites of purine metabolism, especially uric acid (P12) and inosine (P13), may denote their potential as targeted biomarkers related to experimental asthma. The decreased plasma uric acid (P12) suggested that inflammation responses of allergic asthma inhibited the activity of xanthine oxidase in purine metabolism, and manifested the severity of asthma exacerbation. The increased level of inosine (P13) suggests that inflammatory cells induce adenosine triphosphate (ATP) breakdown, resulting in excessive expression of adenosine deaminase (ADA) in the formation of allergic asthma. These findings provided a novel perspective on the metabolites signatures related to allergic asthma, which provided us with new insights into the pathogenesis of asthma, and the discovery of targets for clinical diagnosis and treatment.
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PMID:Aberrant purine metabolism in allergic asthma revealed by plasma metabolomics. 2674 88